Trial Outcomes & Findings for Evaluation of Xiaflex: Trial of Effectivenss iN Dupuytren's (NCT NCT02725528)

NCT ID: NCT02725528

Last Updated: 2023-07-18

Results Overview

Michigan Hand Outcomes Questionnaire (MHQ). Converted to a score rated 0-100 (where higher scores represent better function).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 22 participants
• Primary outcome timeframe: 1 year
• Results posted on: 2023-07-18

Participant Flow

Participant milestones

Measure	Collagenase Injection This procedure was performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this was a pragmatic study, if injection was required in more than one digit, this was done, as per standard of care. The patient's affected hand was prepped with antiseptic solution. Using a hubless syringe with 0.01 mL graduations and a permanently fixed 26- or 27-gauge ½ inch needle the required amount of reconstituted collagenase clostridium histolyticum was withdrawn as follows: 1. Cord affecting an MP joint, withdraw 0.25 mL of the reconstituted solution; 2. Cord affecting a PIP joint: withdraw 0.20 mL of the reconstituted solution per published guidelines. collagenase injection: injection	Limited Palmar Fasciectomy The Dupuytren's cord was excised in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. The procedure was performed according to the surgeon's preferred technique (i.e., zig-zag Brunner incision or straight incision with z-plasty closure of the skin). Loupe magnification was used in surgery to identify and protect the digital neurovascular bundles. The diseased Dupuytren's fascia (cords) causing the contracture was excised. Contracted ligaments at the PIP joints were released by passive stretching or with knife intraoperatively. A plaster splint was applied at the discretion of the surgeon. limited palmar fasciectomy: surgery
Overall Study STARTED	8	14
Overall Study COMPLETED	7	9
Overall Study NOT COMPLETED	1	5

Reasons for withdrawal

Measure	Collagenase Injection This procedure was performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this was a pragmatic study, if injection was required in more than one digit, this was done, as per standard of care. The patient's affected hand was prepped with antiseptic solution. Using a hubless syringe with 0.01 mL graduations and a permanently fixed 26- or 27-gauge ½ inch needle the required amount of reconstituted collagenase clostridium histolyticum was withdrawn as follows: 1. Cord affecting an MP joint, withdraw 0.25 mL of the reconstituted solution; 2. Cord affecting a PIP joint: withdraw 0.20 mL of the reconstituted solution per published guidelines. collagenase injection: injection	Limited Palmar Fasciectomy The Dupuytren's cord was excised in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. The procedure was performed according to the surgeon's preferred technique (i.e., zig-zag Brunner incision or straight incision with z-plasty closure of the skin). Loupe magnification was used in surgery to identify and protect the digital neurovascular bundles. The diseased Dupuytren's fascia (cords) causing the contracture was excised. Contracted ligaments at the PIP joints were released by passive stretching or with knife intraoperatively. A plaster splint was applied at the discretion of the surgeon. limited palmar fasciectomy: surgery
Overall Study Lost to Follow-up	1	4
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Collagenase Injection n=8 Participants This procedure will be performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this is a pragmatic study there may be more than one digit injected at a time just as surgery occurs on more than one digit at a time. A recently published study by Gaston et al confirmed that two concurrent injections of collagenase to 2 affected joints in the same hand are generally well tolerated and the frequency of most adverse events (AEs) is similar to those reported in studies that use single sequential injections. collagenase injection: injection	Limited Palmar Fasciectomy n=13 Participants The Dupuytren's cord will be excised under local anesthesia in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. As this is a pragmatic study comparison of collagenase injections (novel intervention) to limited palmar fasciectomy as it is actually presently performed in all settings academic or community (local in minor room or general/local anesthetic in the main operating room) will be examined. Surgery will be performed according to the operating surgeon's preferred technique i.e. zig-zag Brunner incision or straight incision with z-plasty closure of the skin. limited palmar fasciectomy: surgery	Total n=21 Participants Total of all reporting groups
Age, Continuous	65.8 years STANDARD_DEVIATION 10.2 • n=8 Participants	65 years STANDARD_DEVIATION 9 • n=13 Participants	65.3 years STANDARD_DEVIATION 9.2 • n=21 Participants
Sex: Female, Male Female	1 Participants n=8 Participants	2 Participants n=13 Participants	3 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=8 Participants	11 Participants n=13 Participants	18 Participants n=21 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Canada	8 participants n=8 Participants	13 participants n=13 Participants	21 participants n=21 Participants
Affected Hand Right	6 Participants n=8 Participants	9 Participants n=13 Participants	15 Participants n=21 Participants
Affected Hand Left	2 Participants n=8 Participants	4 Participants n=13 Participants	6 Participants n=21 Participants
Affected Digit Little	2 Participants n=8 Participants	8 Participants n=13 Participants	10 Participants n=21 Participants
Affected Digit Ring	1 Participants n=8 Participants	3 Participants n=13 Participants	4 Participants n=21 Participants
Affected Digit Long	1 Participants n=8 Participants	0 Participants n=13 Participants	1 Participants n=21 Participants
Affected Digit Little & Ring	4 Participants n=8 Participants	0 Participants n=13 Participants	4 Participants n=21 Participants
Affected Digit Long & Little	0 Participants n=8 Participants	1 Participants n=13 Participants	1 Participants n=21 Participants
Affected Digit Little, Ring & Long	0 Participants n=8 Participants	1 Participants n=13 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: 1 year

Michigan Hand Outcomes Questionnaire (MHQ). Converted to a score rated 0-100 (where higher scores represent better function).

Outcome measures

Measure	Collagenase Injection n=7 Participants This procedure will be performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this is a pragmatic study there may be more than one digit injected at a time just as surgery occurs on more than one digit at a time. A recently published study by Gaston et al confirmed that two concurrent injections of collagenase to 2 affected joints in the same hand are generally well tolerated and the frequency of most adverse events (AEs) is similar to those reported in studies that use single sequential injections. collagenase injection: injection	Limited Palmar Fasciectomy n=9 Participants The Dupuytren's cord will be excised under local anesthesia in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. As this is a pragmatic study comparison of collagenase injections (novel intervention) to limited palmar fasciectomy as it is actually presently performed in all settings academic or community (local in minor room or general/local anesthetic in the main operating room) will be examined. Surgery will be performed according to the operating surgeon's preferred technique i.e. zig-zag Brunner incision or straight incision with z-plasty closure of the skin. limited palmar fasciectomy: surgery
Health-related Quality of Life (HRQL) Using the Michigan Hand Outcomes Questionnaire (MHQ)	78.1 units on a scale Standard Deviation 14.9	68.3 units on a scale Standard Deviation 15.7

SECONDARY outcome

Timeframe: 1 year

Population: Missing data addressed by using available case analysis. Difference from flow chart due to participant's loss to follow up. Number of participant's in limited palmar fasciectomy group includes 1 additional participant who completed this outcome, but did not complete the primary outcome as indicated in the participant flow chart.

Health Utility Index Mark 3 (HUI3) of Health. The HUI3 is a generic multi-attribute health-status classification instrument composed of eight attributes or dimensions: vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain with five or six levels per attribute. Dimensions are combined to produce one health utility score. The HUI3 produces health utilities anchored at 0 (minimum) for equal to being dead and 1 (maximum) for perfect health.

Outcome measures

Measure	Collagenase Injection n=7 Participants This procedure will be performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this is a pragmatic study there may be more than one digit injected at a time just as surgery occurs on more than one digit at a time. A recently published study by Gaston et al confirmed that two concurrent injections of collagenase to 2 affected joints in the same hand are generally well tolerated and the frequency of most adverse events (AEs) is similar to those reported in studies that use single sequential injections. collagenase injection: injection	Limited Palmar Fasciectomy n=10 Participants The Dupuytren's cord will be excised under local anesthesia in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. As this is a pragmatic study comparison of collagenase injections (novel intervention) to limited palmar fasciectomy as it is actually presently performed in all settings academic or community (local in minor room or general/local anesthetic in the main operating room) will be examined. Surgery will be performed according to the operating surgeon's preferred technique i.e. zig-zag Brunner incision or straight incision with z-plasty closure of the skin. limited palmar fasciectomy: surgery
HRQL Measured With the Health Utility Index Mark 3 (HUI3) of Health	0.8 units on a scale Standard Deviation 0.79	0.79 units on a scale Standard Deviation 0.14

SECONDARY outcome

Timeframe: 1 year

Population: Missing data addressed by using available case analysis. Difference from flow chart due to incomplete data collection for this outcome (i.e. loss to follow up).

Unité Rhumatologique des Affections de la Main (URAM). The URAM is a disease-specific HRQL measure developed for Dupuytren's Disease (DD) and is composed of a 9-item patient-reported questionnaire. Each item is scored between 0 and 5 depending on the difficulty in performing that particular function with total scores for DD-associated disability ranging from 0 (best) to 45 (worst). High scores suggest high levels of disability and disturbance. The URAM scale is a 1-domain outcome measure postulated to be related to disability associated with DD.

Outcome measures

Measure	Collagenase Injection n=5 Participants This procedure will be performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this is a pragmatic study there may be more than one digit injected at a time just as surgery occurs on more than one digit at a time. A recently published study by Gaston et al confirmed that two concurrent injections of collagenase to 2 affected joints in the same hand are generally well tolerated and the frequency of most adverse events (AEs) is similar to those reported in studies that use single sequential injections. collagenase injection: injection	Limited Palmar Fasciectomy n=9 Participants The Dupuytren's cord will be excised under local anesthesia in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. As this is a pragmatic study comparison of collagenase injections (novel intervention) to limited palmar fasciectomy as it is actually presently performed in all settings academic or community (local in minor room or general/local anesthetic in the main operating room) will be examined. Surgery will be performed according to the operating surgeon's preferred technique i.e. zig-zag Brunner incision or straight incision with z-plasty closure of the skin. limited palmar fasciectomy: surgery
HRQL Measured With the Unité Rhumatologique Des Affections de la Main (URAM)	4.6 units on a scale Standard Deviation 9.2	5.2 units on a scale Standard Deviation 7.6

SECONDARY outcome

Timeframe: 1 year

Population: Missing data addressed by using available case analysis. Difference from flow chart due to incomplete data collection for this outcome (i.e. loss to follow up). Number of participant's in limited palmar fasciectomy group includes 1 additional participant who completed this outcome, but did not complete the primary outcome as indicated in the participant flow chart.

The SDSS is disease-specific scoring system developed for Dupuytren's Disease (DD) with 5 domains, each relevant to DD and scored on a five-point scale (no problem, mild inconvenience, modest inconvenience, definitely troublesome, severe problem). The minimum score is 0 and maximum score is 20 with higher scores suggesting higher levels of disability.

Outcome measures

Measure	Collagenase Injection n=6 Participants This procedure will be performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this is a pragmatic study there may be more than one digit injected at a time just as surgery occurs on more than one digit at a time. A recently published study by Gaston et al confirmed that two concurrent injections of collagenase to 2 affected joints in the same hand are generally well tolerated and the frequency of most adverse events (AEs) is similar to those reported in studies that use single sequential injections. collagenase injection: injection	Limited Palmar Fasciectomy n=10 Participants The Dupuytren's cord will be excised under local anesthesia in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. As this is a pragmatic study comparison of collagenase injections (novel intervention) to limited palmar fasciectomy as it is actually presently performed in all settings academic or community (local in minor room or general/local anesthetic in the main operating room) will be examined. Surgery will be performed according to the operating surgeon's preferred technique i.e. zig-zag Brunner incision or straight incision with z-plasty closure of the skin. limited palmar fasciectomy: surgery
HRQL Measured With the Southampton Dupuytren's Scoring Scheme (SDSS)	6.5 units on a scale Standard Deviation 3.2	7.2 units on a scale Standard Deviation 3.7

SECONDARY outcome

Timeframe: 1 year

Population: Missing data addressed by using available case analysis. Difference from flow chart due to incomplete data collection for this outcome (i.e. loss to follow up). Number of participant's in limited palmar fasciectomy group includes 1 additional participant who completed this outcome, but did not complete the primary outcome as indicated in the participant flow chart.

QALY was calculated by multiplying the difference between quality of life, as measured by the HUI-3 score before and after the intervention by the remaining years of life of the average patient (i.e., life expectancy - patient's age). Life expectancy was set at 79 years for males, and 84 years for females. Higher QALYs represent improved (better) patient outcomes.

Outcome measures

Measure	Collagenase Injection n=7 Participants This procedure will be performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this is a pragmatic study there may be more than one digit injected at a time just as surgery occurs on more than one digit at a time. A recently published study by Gaston et al confirmed that two concurrent injections of collagenase to 2 affected joints in the same hand are generally well tolerated and the frequency of most adverse events (AEs) is similar to those reported in studies that use single sequential injections. collagenase injection: injection	Limited Palmar Fasciectomy n=10 Participants The Dupuytren's cord will be excised under local anesthesia in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. As this is a pragmatic study comparison of collagenase injections (novel intervention) to limited palmar fasciectomy as it is actually presently performed in all settings academic or community (local in minor room or general/local anesthetic in the main operating room) will be examined. Surgery will be performed according to the operating surgeon's preferred technique i.e. zig-zag Brunner incision or straight incision with z-plasty closure of the skin. limited palmar fasciectomy: surgery
Quality Adjusted Life Years (QALY) Measured With the Health Utility Index Mark 3 (HUI3)	0.83 quality-adjusted life years Standard Deviation 1.7	0.93 quality-adjusted life years Standard Deviation 2.8

SECONDARY outcome

Timeframe: 1-4 years

Reccurence was measured as whether or not participants received a repeat diagnosis of Dupuytren's disease with loss of finger extension at the site of prior intervention and underwent palmar fasciectomy (following the collagenase injection or as a revision operation) after initial study treatment. The time horizon for recurrence was between 1-4 years post initial study treatment. Outcome was dichotomous (i.e., recurrence; yes or no).

Outcome measures

Measure	Collagenase Injection n=7 Participants This procedure will be performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this is a pragmatic study there may be more than one digit injected at a time just as surgery occurs on more than one digit at a time. A recently published study by Gaston et al confirmed that two concurrent injections of collagenase to 2 affected joints in the same hand are generally well tolerated and the frequency of most adverse events (AEs) is similar to those reported in studies that use single sequential injections. collagenase injection: injection	Limited Palmar Fasciectomy n=9 Participants The Dupuytren's cord will be excised under local anesthesia in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. As this is a pragmatic study comparison of collagenase injections (novel intervention) to limited palmar fasciectomy as it is actually presently performed in all settings academic or community (local in minor room or general/local anesthetic in the main operating room) will be examined. Surgery will be performed according to the operating surgeon's preferred technique i.e. zig-zag Brunner incision or straight incision with z-plasty closure of the skin. limited palmar fasciectomy: surgery
Recurrence Rates	3 Participants	1 Participants

SECONDARY outcome

Timeframe: 1 year

Passive range of motion degree of extension was measured using a goniometer. Difference in degree, as measured by a goniometer, between the participant's resting maximum extension of the metacarpal-phalangeal joint, relative to a metacarpal-phalangeal joint at full extension (i.e., 0 degrees)

Outcome measures

Measure	Collagenase Injection n=7 Participants This procedure will be performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this is a pragmatic study there may be more than one digit injected at a time just as surgery occurs on more than one digit at a time. A recently published study by Gaston et al confirmed that two concurrent injections of collagenase to 2 affected joints in the same hand are generally well tolerated and the frequency of most adverse events (AEs) is similar to those reported in studies that use single sequential injections. collagenase injection: injection	Limited Palmar Fasciectomy n=9 Participants The Dupuytren's cord will be excised under local anesthesia in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. As this is a pragmatic study comparison of collagenase injections (novel intervention) to limited palmar fasciectomy as it is actually presently performed in all settings academic or community (local in minor room or general/local anesthetic in the main operating room) will be examined. Surgery will be performed according to the operating surgeon's preferred technique i.e. zig-zag Brunner incision or straight incision with z-plasty closure of the skin. limited palmar fasciectomy: surgery
Loss of Extension MCP	20 Degrees Standard Deviation 26.9	2.56 Degrees Standard Deviation 3.97

SECONDARY outcome

Timeframe: 1 year

Population: Missing data addressed by using available case analysis. Difference from flow chart due to incomplete data collection for this outcome (i.e. loss to follow up).

Passive range of motion degree of extension was measured using a goniometer. Difference in degree, as measured by a goniometer, between the participant's resting maximum extension of the proximal inter-phalangeal joint, relative to a proximal inter-phalangeal joint at full extension (i.e., 0 degrees)

Outcome measures

Measure	Collagenase Injection n=5 Participants This procedure will be performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this is a pragmatic study there may be more than one digit injected at a time just as surgery occurs on more than one digit at a time. A recently published study by Gaston et al confirmed that two concurrent injections of collagenase to 2 affected joints in the same hand are generally well tolerated and the frequency of most adverse events (AEs) is similar to those reported in studies that use single sequential injections. collagenase injection: injection	Limited Palmar Fasciectomy n=9 Participants The Dupuytren's cord will be excised under local anesthesia in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. As this is a pragmatic study comparison of collagenase injections (novel intervention) to limited palmar fasciectomy as it is actually presently performed in all settings academic or community (local in minor room or general/local anesthetic in the main operating room) will be examined. Surgery will be performed according to the operating surgeon's preferred technique i.e. zig-zag Brunner incision or straight incision with z-plasty closure of the skin. limited palmar fasciectomy: surgery
Loss of Extension PIP	23.2 Degrees Standard Deviation 18.17	17.2 Degrees Standard Deviation 21.81

SECONDARY outcome

Timeframe: 1 year

Population: Missing data addressed by using available case analysis. Difference from flow chart due to incomplete data collection for this outcome (i.e. loss to follow up).

Passive range of motion degree of extension was measured using a goniometer. Difference in degree, as measured by a goniometer, between the participant's resting maximum extension of the distal inter-phalangeal joint, relative to a distal inter-phalangeal joint at full extension (i.e., 0 degrees)

Outcome measures

Measure	Collagenase Injection n=1 Participants This procedure will be performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this is a pragmatic study there may be more than one digit injected at a time just as surgery occurs on more than one digit at a time. A recently published study by Gaston et al confirmed that two concurrent injections of collagenase to 2 affected joints in the same hand are generally well tolerated and the frequency of most adverse events (AEs) is similar to those reported in studies that use single sequential injections. collagenase injection: injection	Limited Palmar Fasciectomy n=2 Participants The Dupuytren's cord will be excised under local anesthesia in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. As this is a pragmatic study comparison of collagenase injections (novel intervention) to limited palmar fasciectomy as it is actually presently performed in all settings academic or community (local in minor room or general/local anesthetic in the main operating room) will be examined. Surgery will be performed according to the operating surgeon's preferred technique i.e. zig-zag Brunner incision or straight incision with z-plasty closure of the skin. limited palmar fasciectomy: surgery
Loss of Extension DIP	8 Degrees Standard Deviation 0	10 Degrees Standard Deviation 14.14

Adverse Events

Collagenase Injection

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Limited Palmar Fasciectomy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Achilles Thoma

McMaster University

Phone: 905-523-0019

Email: athoma@mcmaster.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place